Currently, there is a wealth of basic research evidence for the pathophysiological bases of neurodegenerative disorders that serves as a guide for the development of therapeutic strategies. However, there is a tight bottleneck that exists in the translation of this information into clinical practice. One cause of this bottleneck is the lack of specific and reliable biomarkers of disease that serve to expedite clinical trials and identify agents that have the most promise as disease-modifying drugs. Utilization of biomarkers of disease would make clinical trials faster, less expensive and more powerful. Therefore, I am focusing my academic career on translational research that will serve to identify biomarkers of neurodegenerative diseases, optimize clinical trials and provide a better understanding of the underlying pathophysiological bases for these disorders. I propose to accomplish this goal by examining the utility of [18F] FDDNP, a radiolabeled marker of abnormal protein aggregates, to identify intraneuronal aggregates in humans with symptomatic and pre-symptomatic HD and in HD transgenic rats. Pre-clinical studies in rats and clinical trials in humans of potentially therapeutic compounds will then be carried out using [18F] FDDNP. Huntington disease (HD), is an ideal disorder to carry out these objectives as the mutation has been identified, animal models generated and mechanisms of disease studied and found to be similar to many other disorders including Parkinson disease, Alzheimer disease and additional CAG repeat expansion diseases. Thus, results from the proposed research can be applied broadly to the treatment of neurological disease. I have a background in the basic science research of neurodegenerative processes and clinical sub-specialty training in the field of movement disorders. As a new faculty member in the UCLA Neurology department, I now have access to state-of-the-art resources and world-renowned collaborators that make this translational research project possible. Translational research is imperative to expedite the development of effective treatments for fatal neurodegenerative diseases. This project serves to identify techniques that will streamline the process of this development by facilitating pre-clinical and clinical trials of potential therapeutic compounds. [unreadable]